====== Complement Inhibitors ======

Complement inhibitors are targeted immune therapies that block overactivation of the complement cascade.

They are used in diseases driven by complement-mediated tissue injury.

See physiology:
  * [[immunology:complement_system|Complement System]]

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===== Mechanistic Targets =====

Complement inhibitors act at different levels of the cascade:

  * C3 inhibition
  * C5 inhibition
  * C5a receptor blockade

Blocking complement reduces:

  * Hemolysis
  * Inflammation
  * Membrane attack complex formation

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===== C5 Inhibitors =====

These block cleavage of C5 → prevent:

  * C5a (anaphylatoxin)
  * C5b-9 (MAC)

Drugs:

  * [[immunology:biologics:eculizumab|Eculizumab]]
  * [[immunology:biologics:ravulizumab|Ravulizumab]]

Indications:

  * Paroxysmal nocturnal hemoglobinuria (PNH)
  * Atypical hemolytic uremic syndrome (aHUS)
  * Generalized myasthenia gravis
  * Neuromyelitis optica spectrum disorder

Key risk:
  * Increased risk of Neisseria infection

Vaccination required before initiation.

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===== C3 Inhibitors =====

Block upstream C3 activation.

Drug:

  * [[immunology:biologics:pegcetacoplan|Pegcetacoplan]]

Effect:

  * Prevents opsonization (C3b)
  * Prevents downstream C5 activation

Used in:
  * Paroxysmal nocturnal hemoglobinuria

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===== C5a Receptor Inhibitors =====

Block inflammatory signaling of C5a.

Drug:

  * [[immunology:biologics:avacopan|Avacopan]]

Used in:

  * ANCA-associated vasculitis

Mechanism:

  Blocks C5a-mediated neutrophil activation without blocking MAC formation.

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===== Clinical Integration =====

Complement overactivation contributes to:

  * [[hematology:clinical:paroxysmal_nocturnal_hemoglobinuria|Paroxysmal Nocturnal Hemoglobinuria]]
  * [[nephrology:clinical:atypical_hemolytic_uremic_syndrome|Atypical HUS]]
  * [[rheumatology:clinical:anca_associated_vasculitis|ANCA-Associated Vasculitis]]
  * Neuromyelitis optica

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===== High-Yield Summary =====

  * C5 inhibitors block MAC formation.
  * C3 inhibitors block all downstream complement activity.
  * C5a receptor inhibitors block inflammation but preserve MAC.
  * Major risk: meningococcal infection.
  * Vaccinate before starting therapy.